A one-stage procedure is nowadays often used for implanting orthopaedic or dental implants, generally metallic implants, into bone tissue.
In the one-stage procedure, a first implant part, such as a dental fixture, is surgically placed into the bone tissue, and a healing cap or a secondary implant part, such as an abutment, is then attached to the first implant part directly after the surgical operation. The soft tissue is thereafter allowed to heal around the healing cap or the secondary implant part. When a healing cap is used, the cap is removed after a few weeks or months without any surgical procedure, and secondary implant parts, such as an abutment and a provisional crown, are attached to the first implant part. The one-stage procedure is for instance described in L Cooper et al: “A multicenter 12-month evaluation of single-tooth implants restored 3 weeks after 1-stage surgery”, The International Journal of Oral & Maxillofacial Implants, Vol 16, No 2 (2001).
The two-stage procedure, which is another known implantation procedure, involves in a first stage surgically placing a first implant part, such as a dental fixture, into the bone tissue, where it is then allowed to rest unloaded and immobile for a healing period of three months or more in order to allow the bone tissue to grow onto the implant surface to permit the implant to be well attached to the bone tissue, the cut in the soft tissue covering the implant site being allowed to heal over the implant, and in a second stage opening the soft tissue covering the implant and attaching secondary implant parts, such as a dental abutment and/or a restoration tooth, to the first implant part, such as said fixture, forming the final implant structure. This procedure is for instance described by Brånemark et al: “Osseointegrated Implants in the Treatment of the Edentulous Jaw, Experience from a 10-year period”, Almquist & Wiksell International, Stockholm, Sweden.
However, the fact that the implant not should be loaded during the healing period means that the secondary implant parts may not be attached to the first implant part and/or used during the healing period of three months or more. In view of the discomfort associated with this, it is desirable to minimize the time period necessary for the above-mentioned first stage or even perform the entire implantation procedure in a single operation, i.e. to use the one-stage procedure.
For some patients, it might be considered better to wait at least three months before functionally loading the implant, both for one- and two-stage procedures. However, an alternative using the one-stage procedure is to put the implant in function directly after implantation (immediate loading) or a few weeks after implantation (early loading). These procedures are, for instance, described by D M Esposito, pp 836-837, in Titanium in Medicine, Material Science, Surface Science, Engineering, Biological Responses and Medical Application, Springer-Verlag (2001).
It is essential that the implant establishes a sufficient stability and bond between implant and bone tissue to enable the above disclosed immediate or early loading of the implant. It shall also be noted that an immediate or early loading of the implant may be beneficial to bone formation.
Some of the metals or alloys, such as titanium, zirconium, hafnium, tantalum, niobium, or alloys thereof, that are used for bone implants are capable of forming a relatively strong bond with the bone tissue, a bond which may be as strong as the bone tissue per se, sometimes even stronger. The most notable example of this kind of metallic implant material is titanium and alloys of titanium whose properties in this respect have been known since about 1950. This bond between the metal and the bone tissue has been termed “osseointegration” (Albrektsson T, Brånemark P I, Hansson H A, Lindström J, “Osseointegrated titanium implants. Requirements for ensuring a long-lasting, direct bone anchorage in man”, Acta Orthop Scand, 52:155-170 (1981)).
It may be noted that in contact with oxygen, titanium, zirconium, hafnium, tantalum, niobium and their alloys are instantaneously covered with a thin oxide layer. This native oxide layer on titanium implants mainly consists of titanium(IV) dioxide (TiO2) with minor amounts of Ti2O3, TiO and Ti3O4.
Although the bond between the (oxidised) metal, e.g. titanium, and the bone tissue may be comparatively strong, it is desirable to enhance this bond.
There are to date several methods for treating metallic implants in order to obtain a better attachment of the implant, and thus improved osseointegration. Some of these involve altering the morphology of the implant, for example by creating irregularities on the implant surface in order to increase the surface roughness in comparison to an untreated surface. It is believed that an increased surface roughness, which gives a larger contact and attachment area between the implant and the bone tissue, provides a better mechanical retention and strength between implant and bone. It is well-known within the art that a surface roughness can be provided by, for example, plasma spraying, blasting or acid etching.
Other methods for obtaining a better attachment of the implant to the bone tissue involve alteration of the chemical properties of the implant surface.
Several methods involve the application of a layer of ceramic material, such as hydroxyapatite, to the implant surface, inter alia in order to improve the bonding of the implant to bone since hydroxyapatite is chemically related to bone. A disadvantage with ceramic coatings is, however, that they may be brittle and may flake or break off from the implant surface, which may in turn lead to an ultimate failure of the implant.
Other methods for altering the chemical properties of the implant involve application of fluorine and/or fluoride on the implant surface (WO 94/13334, WO 95/17217, WO 04/008983, and WO 04/008984).
It is known from, for instance, U.S. Pat. No. 4,917,702, U.S. Pat. No. 5,441,536, WO 99/53971, WO 03/039609 and EP 1481696, to incorporate certain ions, such as Mg2+, Ca2+, Mn2+ or Sr2+, in calcium phosphate-containing coatings, such as hydroxyapatite, applied on implants in order to promote bone growth onto the implant.
For instance, WO 01/49327 and Ni G X et al, “Strontium-Containing Hydroxyapatite (Sr-HA) Bioactive Cement for Primary Hip Replacement: An In Vivo Study”, Inc J Biomed Mater Res Part B: Appl Biomater 77B, pp 409-415 (2006); Ni et al disclose bioactive bone cements including strontium-containing hydroxyapatite.
Xue W, et al, “Osteoprecursor Cell Response to Strontium-Containing Hydroxyapatite Ceramics”, J Biomed Mater Res A, 79(4), pp 804-814 (2006), shows that Sr-containing hydroxyapatite has a greater ability to induce apatite precipitation than hydroxyapatite and that strontium stimulates osteoprecursor cell (OPC1) differentiation.
In addition, EP 1023910 describes a hydroxylated and hydrophilic implant enclosed in a sealed container comprising, for instance, pure water and divalent cations, such as Mg2+, Mn2+ or Sr2+. These cations are said to adsorb on the oxide layer of the implant.
WO 2006/004297 discloses an osseoinductive metal implant, such as titanium or an alloy thereof, comprising a layer of metal oxide and a layer of a bio-active material composed of any one or more of Li, Na, K, Rb, Cs, Fr, Mg, Ca, Sr, Ba, Ra, Sc, Y, Lu, Ti, Zr, Hf, Nb, Ta, Cr, Mo, W, Mn, Re, Fe, Ru, Os, Co, Rh, Ir, Ni, Pd, Pt, Cu, Ag, Au, Zn, Ga, In, Ti, Sn and Bi formed thereon. Said layer of a bio-active material is formed by implanting the ionized bio-active material into the surface of said metal oxide. A working example is, however, only described for a titanium implant comprising incorporated ionized calcium in its titanium oxide layer.
Mention can also be made of WO 2002/096475 referring to a titanium implant comprising calcium, phosphor or sulphur in the titanium oxide layer, and WO 2005/084577 referring to a titanium implant comprising magnesium in the titanium oxide layer.
Although implants which provide a comparatively strong bond between the implant surface and the bone exist, there is a need in the art to enhance this bond, i.e. to improve the “osseointegration” process of an implant in bone tissue.
Thus, there is a need in the art to provide an implant having a desired rate of attachment and which has the ability to form a mechanically strong bond between the bone and the implant upon implantation thereof in bone tissue.